SWITCHIII: Switching From Fondaparinux to Bivalirudin or Unfractionated Heparin in ACS Patients Undergoing PCI

• Sponsor: Medstar Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00464087
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 100
• Locations: 7
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of this clinical trial is to evaluate safety of switching from fondaparinux to either unfractionated heparin or bivalirudin for patients experiencing acute coronary syndrome undergoing percutaneous coronary angioplasty.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndromes	Drug: Switching from Fondaparinux to Bivalirudin or Unfractionated Heparin	Phase 3

Detailed Description

This is a prospective open label, randomized, multi-center registry. One hundred patients who received fondaparinux within the 24 hours prior to presentation to the coronary catheterization lab and who are suitable for percutaneous coronary intervention. The patients will be randomized in a 1:1 fashion to either unfractionated heparin or bivalirudin during the angioplasty. All patients will be followed throughout the duration of the hospital stay.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Switching From Arixtra (Fondaparinux) to Angiomax (Bivalirudin) or Unfractionated Heparin in Patients With Acute Coronary Syndromes (ACS) Without ST-segment Elevation Undergoing Percutaneous Coronary Intervention (PCI): SWITCH III
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Heparin Patients are switched from fondaparinux to heparin, receiving a dose of 60 U/Kg IV during the PCI	Drug: Switching from Fondaparinux to Bivalirudin or Unfractionated Heparin
Active Comparator: Bivalirudin Patients switched from fondaparinux to bivalirudin, received a bolus of 0.75 mg/kg IV followed by infusion of 1.75 mg/g per hour infusion during the PCI.	Drug: Switching from Fondaparinux to Bivalirudin or Unfractionated Heparin

Outcome Measures

Primary Outcome Measures

1. The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge [During hospitalization, after Fondaparinux administration, prior to randomization]

   Characterized as Fatal bleed, Major bleed (SWITCH III criteria) or major bleed (OASIS criteria)

2. The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge [During hospitalization, after randomization, during PCI]

   Categorized as Fatal bleed, major bleed (SWITCH III criteria) or major bleed (OASIS criteria)

3. The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge [During hospitalization, after PCI]

   Characterized as fatal bleed, major bleed (SWITCH III criteria) or major bleed (OASIS criteria)

Secondary Outcome Measures

1. Secondary in Hospital Endpoint Will be In-hospital Death (Non-hemorrhagic Related), Vascular Access Site Complications, Myocardial Infarction, Need for Repeat Revascularization, Procedural Complication and Catheter Thrombosis [during index hospitalization]

   Characterized as death, access site complication, access site thrombus, hematoma, myocardial infarction, repeat vascularization, dissection, stent thrombosis, catheter thrombosis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The patient is, male or female, > 18 years of age; 2. The patient presents with coronary syndrome, unstable angina or non ST segment elevated myocardial infarction (NSTEMI) defined as at least one of the following criteria:

• Elevated creatine kinase MB or Troponin I or T (above ULN)

• ECG changes indicative of ischemia 3. The patient is scheduled for angiography, with possible angioplasty, evaluation of their coronary disease; 4. The patient is able and willing to conform to the requirements of the study and voluntarily signs an Informed Consent.

1. ST elevated myocardial infarction within the preceding 48 hours;

2. Patient weighs more than 400 lbs (181.2 kg) or less than 110 lbs (50 kg);

3. Patients presenting on or received bivalirudin, GP IIb/IIIa inhibitors or low-molecular weight heparin within the preceding 24 hours;

4. Patients that received unfractionated heparin less than or equal to 90 minutes prior to fondaparinux administration.

5. Patients with known conditions of bleeding diathesis or actively bleeding within the previous 6 months (GI bleed etc.);

6. Known diagnosis of acute bacterial endocarditis;

7. Patients with cardiogenic shock or required intra-aortic balloon pump (IABP)

8. If patient is on warfarin (Coumadin) therapy;

9. Patients who had a major or minor stroke (CVA or TIA) or major surgery within the past 6 months;

10. Known impaired renal function (creatinine ≥ 3.0 mg/dL (265.2 μmol/L),) status post renal transplant, patients on chronic dialysis or creatinine clearance ≤ 30 ml/min;

11. A platelet count of less than 100,000 cells/mm3;

12. Known allergies to fondaparinux, aspirin, clopidogrel bisulfate (PlavixR), ticlopidine (TiclidR), heparin, bivalirudin, or contrast that cannot be medically managed;

13. Prior angioplasty within the previous 30 days;

14. Contraindication to low-molecular weight heparin, unfractionated heparin or bivalirudin;

15. Pregnant or lactating women;

16. Any significant medical condition, which in the investigator's opinion, may interfere with the patient's optimal participation in the study;

17. Currently participating in an investigational drug or another device study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bridgeport Hospital	Bridgeport	Connecticut	United States	06610
2	Washington Hospital Center	Washington	District of Columbia	United States	20010
3	Baptist Cardiac and Vascular Institute	Miami	Florida	United States	33176
4	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
5	University of North Carolina-Chapel Hill	Chapel Hill	North Carolina	United States	27599
6	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L2X2
7	Institut Universitaire de cardiologie et de Pneumologie de Québec (Hôpital Laval)	Québec City	Quebec	Canada	G1V 4G5

Sponsors and Collaborators

• Medstar Health Research Institute
• GlaxoSmithKline

Investigators

• Principal Investigator: Ron Waksman, MD, Washington Hospital Center, Washington, DC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT00464087
• Other Study ID Numbers: SWITCH III
• First Posted: Apr 20, 2007
• Last Update Posted: Aug 1, 2013
• Last Verified: Jul 1, 2013

• Additional relevant MeSH terms: Acute Coronary Syndrome; Syndrome; Heparin; Calcium heparin; PENTA; Bivalirudin; Fondaparinux

Study Results

Participant Flow

Pre-assignment Detail	Patients who were enrolled and received fondaparinux and who did not have sufficient disease requiring any revascularization procedure will be followed through the duration of the hospitalization. Patients will have a complete blood count (CBC) prior to discharge. These patients are enrolled, but considered screen failures.

Arm/Group Title	Heparin	Bivalirudin	Screen Failures
Arm/Group Description	All patients received fondaparinux at a dose of 2.5 mg subcutaneously no more than 24 hours before angioplasty. They are randomized to unfractionated heparin during angioplasty and receive a minimum dose of 60 U/kg IV.	All patients received fondaparinux at a dose of 2.5 mg subcutaneously no more than 24 hours before angioplasty. They are randomized to Bivalirudin during angioplasty and receive a minimum dose of bolus 0.75 mg/kg IV followed by, infusion of 1.75 mg/kg/hr for the duration of the PCI.	These patients were enrolled because they received study drug, but did not have enough disease to require PCI.
Period Title: Overall Study
STARTED	49	51	29
COMPLETED	49	51	0
NOT COMPLETED	0	0	29

Baseline Characteristics

Arm/Group Title	Heparin	Bivalirudin	Screen Failures	Total
Arm/Group Description	unfrationated heparin during angioplasty	bivalirudin during angioplasty	Screen Failures are patients who are enrolled and receive the study drug, but do not have enough disease to have percutaneous coronary intervention.	Total of all reporting groups
Overall Participants	49	51	29	129
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	31 63.3%	27 52.9%	22 75.9%	80 62%
>=65 years	18 36.7%	24 47.1%	7 24.1%	49 38%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.18 (13.36)	63.33 (12.17)	54.45 (13.62)	60.45 (14.42)
Sex: Female, Male (Count of Participants)
Female	18 36.7%	14 27.5%	8 27.6%	40 31%
Male	31 63.3%	37 72.5%	21 72.4%	89 69%
Region of Enrollment (participants) [Number]
United States	16 32.7%	18 35.3%	29 100%	63 48.8%
Canada	33 67.3%	33 64.7%	0 0%	66 51.2%

Outcome Measures

1. Primary Outcome

Title	The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge
Description	Characterized as Fatal bleed, Major bleed (SWITCH III criteria) or major bleed (OASIS criteria)
Time Frame	During hospitalization, after Fondaparinux administration, prior to randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heparin	Bivalirudin	Screen Failures
Arm/Group Description	unfractionated heparin during angioplasty	bivalirudin during angioplasty	Screen Failures are patients who are enrolled and receive the study drug, but do not have enough disease to have percutaneous coronary intervention.
Measure Participants	49	51	0
Number [participants]	0 0%	0 0%

2. Secondary Outcome

Title	Secondary in Hospital Endpoint Will be In-hospital Death (Non-hemorrhagic Related), Vascular Access Site Complications, Myocardial Infarction, Need for Repeat Revascularization, Procedural Complication and Catheter Thrombosis
Description	Characterized as death, access site complication, access site thrombus, hematoma, myocardial infarction, repeat vascularization, dissection, stent thrombosis, catheter thrombosis
Time Frame	during index hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heparin	Bivalirudin
Arm/Group Description	unfractionated heparin during angioplasty	bivalirudin during angioplasty
Measure Participants	49	51
Number [participants]	4 8.2%	4 7.8%

3. Primary Outcome

Title	The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge
Description	Categorized as Fatal bleed, major bleed (SWITCH III criteria) or major bleed (OASIS criteria)
Time Frame	During hospitalization, after randomization, during PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heparin	Bivalirudin	Screen Failures
Arm/Group Description	unfractionated heparin during angioplasty	bivalirudin during angioplasty	Screen Failures are patients who are enrolled and receive the study drug, but do not have enough disease to have percutaneous coronary intervention.
Measure Participants	49	51	0
Number [participants]	0 0%	0 0%

4. Primary Outcome

Title	The Primary Endpoint Will be in Hospital Major Bleed as Defined by the Study Protocol, Assessed at Three Time Points: After Study Drug Administration, But Prior to Randomization;After Randomization During PCI; and After PCI, Prior to Discharge
Description	Characterized as fatal bleed, major bleed (SWITCH III criteria) or major bleed (OASIS criteria)
Time Frame	During hospitalization, after PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heparin	Bivalirudin	Screen Failures
Arm/Group Description	unfractionated heparin during angioplasty	bivalirudin during angioplasty	Screen Failures are patients who are enrolled and receive the study drug, but do not have enough disease to have percutaneous coronary intervention.
Measure Participants	49	51	0
Number [participants]	0 0%	1 2%

Adverse Events

Arm/Group Title	Heparin		Bivalirudin		Screen Failures
Arm/Group Description	unfrationated heparin during angioplasty		bivalirudin during angioplasty		Screen Failures are patients who are enrolled and receive the study drug, but do not have enough disease to have percutaneous coronary intervention.
All Cause Mortality
	Heparin		Bivalirudin		Screen Failures
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Heparin		Bivalirudin		Screen Failures
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		1/51 (2%)		0/0 (NaN)
Vascular disorders
Major Bleed	0/49 (0%)	0	1/51 (2%)	1	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Heparin		Bivalirudin		Screen Failures
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/49 (8.2%)		4/51 (7.8%)		0/0 (NaN)
Cardiac disorders
Dissection	1/49 (2%)	1	1/51 (2%)	1	0/0 (NaN)	0
Ventricular fibrillation	1/49 (2%)	1	0/51 (0%)	0	0/0 (NaN)	0
Repeat revascularization	1/49 (2%)	1	0/51 (0%)	0	0/0 (NaN)	0
Vascular disorders
Access Site Complication	1/49 (2%)	1	3/51 (5.9%)	3	0/0 (NaN)	0

Limitations/Caveats

This trial included only small number of patients and is not powered to detect intergroup differences

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.